Regulatory T cells (Treg) control the autoreactive components of the immune system. Consequently, Treg dysfunction is linked to severe autoimmunity, and compounds that increase Treg numbers or activity are expected to be useful in the treatment of autoimmune disorders such as multiple sclerosis.
Treg cells are a specialized subset of T cells involved in the control of pathogenic autoimmunity (Sakaguchi et al., Ann. Rev. Immunol., 22:531-562, 2004. The importance of Treg for immunoregulation is highlighted by the immune disorders that result from Treg depletion with antibodies (Sakaguchi et al., J. Immunol. 155, 1151-64 (1995)); as a result of the thymectomy of 3 day old newborns (Sakaguchi et al., J Exp Med. 156, 1565-76 (1982)); or treatment with diphtheria toxin in transgenic mice with a Treg-restricted expression of the diphtheria toxin receptor (Kim et al., Nat Immunol. 8, 191-7 (2007)). In addition, Treg deficiencies have been described in several autoimmune diseases such as multiple sclerosis (Viglietta et al., J. Exp. Med. 199, 971-9 (2004)), rheumatoid arthritis (Ehrenstein et al., J Exp Med. 200, 277-85 (2004)), diabetes (Brusko et al., Diabetes. 54, 1407-14 (2005); Lindley et al., Diabetes. 54, 92-9 (2005)), and lupus (Mudd et al., Scand. J. Immunol. 64(3):211-218 (2006)).